Neurexin-neuroligin trans-synaptic interaction in learning and memory

  • Awarded: 2008
  • Award Type: Research
  • Award #: 94173

Autism arises in early childhood, during a period of intense learning when many of the brain’s connections are modified by experience. Eric Kandel, Yun-Beom Choi and Craig Bailey of Columbia University are using animal models of memory formation to investigate how two autism-associated proteins — neuroligin and neurexin — regulate this process.

After initial contact between two neurons, neurexin on the transmitting cell and neuroligin on the receiving cell bind to each other and strengthen signaling across the synapse. Choi, Bailey and Kandel studied a simple form of learned fear in slugs (Aplysia californica) and found that interaction between neurexin and neuroligin across the synapse is important for the induction and stabilization of changes in synaptic connections during learning. As a next step, they plan to investigate candidate proteins that may regulate the translation of neurexin and neuroligin, as well as downstream proteins that are regulated by the interaction between neurexin and neuroligin.

People with autism often have unusual responses to fear in new situations, a feature that correlates with abnormal activity in the amygdala, the brain region that controls fear memory. The researchers propose that these atypical fearful responses reflect abnormal synapses in the amygdala, perhaps due to the loss or change of neuroligin or neurexin and their interaction. Through electrophysiological studies, they have found that acute genetic suppression of neuroligin-1 in the rodent amygdala impairs learning-induced strengthening of synaptic connections. It also leads to a deficit in fear conditioning. Next, the researchers plan to investigate how acute suppression of neurexin in the mouse amygdala affects learning-induced changes in synaptic connections and associated fear memory.

Together, these approaches may reveal how neuroligin and neurexin act in the brain and, in particular, why they are important in autism. This information may be broadly relevant for the disorder, as many mutations linked to autism appear to compromise synaptic strength.

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